The Autism Celloidin Library (ACL)

The ACL is an ATP established collection of age and sex matched, whole hemispheres from both unaffected (control) and autistic individuals representing much of the human lifespan.  Each whole hemisphere has been hardened (fixed in celloidin), carefully sectioned at 200 µm intervals and serially allocated into 3 separate series, by sequentially placing each cut section into one of the three successive groups (i.e. – 1,2,3…1,2,3…).  Each series was then allocated to a separate scientific fate:

• Series 1 – Tissue was stained with Crysl Violet (CV), permanently mounted on glass slides and resides at the Department of Neurobiology, New York State Institute of Brain Research in New York for experimental research, under the stewardship of Jerzy Wegiel, Ph.D.
• Series 2 – Tissue was stained with Gallocianin, permanently mounted on glass slides and resides at the Department of Neuroscience, Mount Sinai School of Medicine in New York for experimental research, under the stewardship of Patrick Hof, MD.
• Series 3 – Tissue was placed in reserve as floating sections in EtOH, awaiting a proper experimental design and steward for its use.

Due to a globally limited availability of brain tissue, a key scientific field of comparative (autism and unaffected) tissue analysis was being hindered.   To address this significant crisis in autism research, the ATP created the ACL - the largest, permanent brain tissue resource for basic neurological studies in autism.  To maximize the scientific potential of this resource, the collection was allocated into three distinct series, each with their own unique experimental attributes.  Working collaboratively with both the stewards of the ACL series and approved researchers, as well as combining the uniqueness of their experimental approaches, the ATP is not only able to greatly stimulate the research efforts of these scientists, but is also able to pool all resulting research data by these researchers and leverage the greatest scientific value from this exceptional collection.

Brain Tissue Genetic Repository

To further characterize brain tissue within its collection, the ATP has established a brain tissue genetic repository from brains donated to the program.  Sample tissue from each selected brain was carefully removed, its DNA isolated, stored in small aliquots and made available to approved researchers.  Additionally, genetic analysis was conducted on each of these samples for both copy number variation (CNV) and small nucleotide polymorphisms (SNP), with all resultant data provided free of charge to researchers accessing this repository.  To date, genetic analysis has been conducted on cortical samples from 50 brains utilizing both 1M Illumina and Affymetrix 6.0 DNA chips.   By providing these isolated DNA samples with “analysis-ready” data to complement the tissue and associated clinical data of brains within its collection, the ATP is taking a unique step forward in helping bridge the gap between genetic research and direct, deeper studies in autism biology through tissue analysis.  This research was conducted in collaboration with and placed under the stewardship of Stephen Scherer, Ph.D. at The Center for Applied Genomics, The Hospital for Sick Children, Toronto, Canada where the repository resides.

Induced Pluripotent Cells (iPC’s) Repository

Only through direct analysis of tissue can one delve deep into the underlying biology of autism.  With the scarcity of donated brain tissue globally, the ATP has sought to supplement its repositories with additional, relevant neurological tissue for scientific discovery.  With the advent of stem cell research, there is now a potential to create a near limitless source of neurological tissue to enhance cell and molecular biology studies in autism.  Though stem cells hold great potential for autism science, this technology has its own limitations and cannot replace the enormous need for brain tissue donations.  However, each of these two fields of research (brain tissue and stem cell), strongly complement one another and jointly, can offer an experimentally strategic approach to rapid discovery.

The ATP is working to help facilitate stem cell discoveries in autism research by utilizing its established international position in autism tissue research and unique resources to curate and steward an autism induced stem cell repository.    Skin samples from individuals with autism are being collected and genetically engineered to induce a “stem cell” or pluripotent state (iPC’s).  These cells can then be coaxed into becoming cells that mimic neuronal cells present within the human brain.   With these newly formed iPC neuronal cells, researchers will be able to study laboratory created “brain cells” in a unique and far more rapid fashion.  Also, with the ability to grow many of these cells within a laboratory, scientists will be nearly free from the constraints of the limited resources indicative of traditional brain tissue research.  Together with brain tissue research, iPC’s offer yet another tool in helping scientists uncover the biological conditions behind autism.

This repository has been established through the work of Philip Schwartz, Ph.D. at the Children’s Hospital of Orange County Human Neural Stem Resource in California in collaboration with Randi J. Hagerman, MD. at the M.I.N.D. Institute, UC Davis in California.

Digital Imaging of the Human Autism Brain

The ATP currently holds the largest collection of human autism brain tissue optimally viable for digital imaging.  To further extend the scientific impact of the ACL series (see above), the ATP is seeking collaborations to help fund 3D, high resolution digital imaging of the ACL series to create an on-line digital brain tissue repository for dissemination of this extraordinary resource for scientific research to researchers worldwide.